The primary role of the Mouse Genetics Core Facility (MGCP) Is to facilitate the use of mouse molecular genetics at MSKCC for in vivo studies of gene functions germane to cancer. Relevant fields where mouse models can be applied include cell growth and behavior, cellular differentiation, embryonic development, immunobiology, genome integrity, and malignant transformation. The MGCP consists of 3 groups: the Transgenic Mouse Group, the Colony Management Group, and the ES Cell Culture Group. Some of the services these groups provide are: (1) Production of transgenic mice: transgene DNA purification, pronuclear injection, genotyping of founder mice, and breeding of positive founders to provide Gl progeny. (2) Gene Targeting: electroporation of gene targeting vector into ES cells, selection and identification of clones, and cryopreservation of targeted ES cell clones. (3) Production of gene targeted mice: generation of chimeric mice by blastocyst Injection and identification of germline chimeras. (4) Long term storage of mouse strains by cryopreservation of sperm or embryos. (5) Rederivation by embryo transfer or IVF for strain importation and recovery. (6) Performance of specialized animal surgical procedures and embryological techniques. (7) Provision of specialized mouse strains/lines for investigators' research. (8) Comprehensive management of research animal colonies for investigators. (9) Genotyping of transgenic, gene targeted, and mutant mouse lines. The services provided by the Mouse Genetics Core has supported the research of 74 investigators in the past year. During the past grant period the work of the Core has contributed to 241 publications of researchers from 8 research programs. For example, the Core provided services to study the relationship between genome integrity and cancer. The Core carried out ES cell injections for the derivation of novel mouse strains in which certain facets of the DNA damage response are impaired by mutation affecting the Mre11 complex, the apical sensor of DNA damage mammals. Collectively, the data obtained led to the publication of work that described the central role of the Mre11 complex in tumor suppression by the DNA damage response.